Type 2 Diabetes ICYMI

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – The use of tricyclic antidepressants (TCAs) conferred the highest risk for a new, first-time clinical fracture in people with type 2 diabetes with overweight or obesity, independent of any prevalent neuropathy, according to findings from an analysis of a large, randomized clinical trial.

Although the findings are suggestive, they don’t definitively pin blame on TCAs, said Rachel Elam, MD, who presented the study at the annual meeting of the American Society for Bone and Mineral Research. “I think that there’s not enough information to conclude that tricyclic antidepressants directly lead to fractures, but I think it opens the door [to] something we should look into more. Is it being mediated by a better predictor, or is it the medication itself? I think it’s more hypothesis generating,” said Dr. Elam, an assistant professor of medicine in the division of rheumatology at the Medical College of Georgia, Augusta.

Patients with type 2 diabetes are known to be at increased risk of fracture, but prediction tools tend to underestimate this risk, Dr. Elam said. “Type 2 diabetes–specific clinical risk factors may be helpful for finding out fracture risk in this population,” Dr. Elam said during her talk.

Glycemic control is one candidate risk factor because advanced glycation end products are linked to reduced bone strength. Other factors include antidiabetic medication use, neuropathy, and microvascular disease, which has been linked to increased cortical porosity.

The study examined a somewhat younger population than previous surveys, having drawn from the Look AHEAD-C clinical trial, which examined the effects of an intensive lifestyle intervention on type 2 diabetes. Look AHEAD-C included 4,697 participants aged 45-75 from 16 U.S. clinical sites. Participants had a body mass index of 25.0 kg/m² or higher and hemoglobin A1c levels of 11% or below.

Dr. Elam cited the database’s inclusion of factors like A1c levels, renal parameters, and diabetic neuropathy. “It gave us a really good population to look at those risk factors” in a large group of people with type 2 diabetes, she said.

Over a median follow-up of 16.6 years, there were 649 participants with incident first clinical fracture(s). Statistically significant factors predicting fracture risk included TCA use (hazard ratio, 2.24; 95% confidence interval, 1.14-4.43), female gender (HR, 2.20; 95% CI, 1.83-2.66), insulin use (HR, 1.26; 95% CI, 1.02-1.57), increases in A1c level (per 1% increase: HR, 1.12; 95% CI, 1.04-1.20), age (HR, 1.02; 95% CI, 1.01-1.04), other or mixed race/ethnicity (HR, 0.68; 95% CI, 0.52-0.87), Hispanic White race/ethnicity (HR, 0.60; 95% CI, 0.39-0.91), non-Hispanic Black race/ethnicity (HR, 0.35; 95% CI, 0.26-0.47), and estrogen use (HR, 0.65; 95% CI, 0.44-0.98).

During the Q&A session following the presentation, Elsa Strotmeyer, PhD, commented that TCAs have been linked to central nervous system pathways in falls in other populations. “It’s a very nice study. It’s important to look at the diabetes complications related to the fracture risk, but I thought that they should have emphasized some more of the diabetes complications being related to fracture rather than these tricyclic antidepressants, because that is not a unique factor to that population,” said Dr. Strotmeyer, who is an associate professor of epidemiology at the University of Pittsburgh.

Instead, she noted a different strength of the study. “The study population is important because they’re a relatively young population with type 2 diabetes, compared to many studies [that] have been published in older populations. Showing similar things that we found in older populations was the unique piece and the important piece of this study,” Dr. Strotmeyer said.

Ultimately, the model wasn’t sufficient to be used as a fall risk predictor, but it should inform future work, according to Dr. Elam. “I think it does lay some new groundwork that when we’re looking forward, it may [help in building] other models to better predict fracture risk in type 2 diabetes. Things that would be important to include [in future models] would be medication use, such as tricyclic antidepressants,” and to make sure we include glycemic control, A1c, and insulin medication.

The study was independently funded. Dr. Elam and Dr. Strotmeyer report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER – In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors as an adjunct to metformin were not associated with an increase in fracture risk, according to a new real-world study.

There have been some reports of an increase in fracture risk associated with SGLT2 inhibitors, and it was observed in the phase 3 CANVAS trial of canagliflozin (Invokana), which led to a Food and Drug Administration warning of fracture risks associated with canagliflozin use. Some ensuing studies did not show an increased risk, but these studies were generally less than a year in duration and may have missed longer-term risk, according to Veerle van Hulten, MSc.

“Fracture risk is something that takes a long time to develop, so we wanted to have a longer follow-up. We looked into the CPRD [Clinical Practice Research Datalink], which is a beautiful database containing real-world data from primary care practices,” said Ms. van Hulten, a PhD student at Maastricht (the Netherlands) University, who presented the study at the annual meeting of the American Society for Bone and Mineral Research.

Ms. van Hulten and colleagues compared SGLT2 inhibitors with dipeptidyl peptidase–4 (DPP-4) inhibitors because the latter are used in similar populations and have been shown to have no effect on fracture risk.

“What we found is that SGLT2 inhibitors are not associated with an increased fracture risk. Even with a duration of use of over 811 days, we did not observe an increased hazard ratio for fractures when compared DPP-4 inhibitor users,” Ms. van Hulten said.

SGLT2 inhibitors reduce blood sugar by increasing elimination of sugar in the urine. They also increase phosphate, reduce calcium, and increase parathyroid hormone, which could in turn negatively affect bone turnover, according to Ms. van Hulten.

In the new study, conducted between January 2013 and June 2020, the researchers used propensity score matching to compare adult patients, including 13,807 who were prescribed SGLT2 inhibitors and 28,524 who were prescribed DPP-4 inhibitors for the first time. They matched patients based on demographics, comorbidities, comedication, and lifestyle factors.

There was no association between SGLT2 inhibitor use and overall fracture risk or major osteoporotic, hip, vertebral, humerus, radius, or ulna fractures. There was no difference in risk for any duration of use, even with the longest duration of use of 811 days (adjusted hazard ratio, 1.0). There were no differences among specific SGLT2 inhibitors, including canagliflozin (aHR, 1.12; 95% confidence interval, 0.73-1.72). Analyses by sex and age also revealed no statistically significant differences between the two drug classes.

During the Q&A session after the presentation, Sarah Berry, MD, MPH, an associate professor of medicine at Harvard Medical School and a clinical researcher at the Marcus Institute for Aging Research, both in Boston, noted the trend toward an increase in fracture risk in the first 90 days. “It looked like there was something going on in the first 90 days, and then after that the results were much closer to the null. I would put out maybe another potential mechanism whereby the SGLT2 inhibitors might cause fracture, and that’s falls. They cause polyuria, and any drug you give that causes women to rush to the bathroom may well cause fractures, particularly in the short term,” Dr. Berry said.

Ms. van Hulten agreed, and also brought up that the drugs can cause osmotic diuresis. That can lead to hypovolemia, the symptoms of which include weakness, fatigue, and dizziness. “And increased falls, of course, increases fracture risk. We do not expect anything to happen to bone metabolism in the first 90 days. I think we can agree that there would be more time needed to alter the bone enough to increase fracture risk, so we expect that this trend toward an increased risk might be attributable to that increased fall risk that might occur with SGLT2 inhibitor use,” she said.

It’s possible that such a mechanism explains increased fracture risk seen in some earlier short-term studies, she added.

Overall, Ms. van Hulten said that the results should provide some confidence in SGLT2 inhibitors, though more work needs to be done. “I think we provide reassurance that SGLT2 inhibitors are safe to use. However, we still only have a median follow-up of 1.6 years. It’s not as long as we maybe would like, but it’s the best we can do with the data available, since the SGLT2 inhibitors have only been used since 2013. So maybe it’s best to prescribe it and keep [fall risk] in mind and look into the effects later on again, but it seems to be safe to use.”

The study received funding from the Novo Nordisk Foundation. Ms. van Hulten and Dr. Berry reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with obesity but without major depressive disorder or suicidal ideation within the previous 2 years attained meaningful weight loss with semaglutide, regardless of antidepressant use at baseline, in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.

Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.  

“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”

“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”

“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”

Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”

“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”

Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.

Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.

Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
 

36,000 Patients with obesity, 500 on antidepressants

Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.

However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.

The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.

The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.

Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m², or ≥27 kg/m² with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m² with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.

They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.

From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
• STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
• STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
• STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%. 

The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
• STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
• STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
• STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.

Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.

The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.

A version of this article appeared on Medscape.com.

Patients with obesity but without major depressive disorder or suicidal ideation within the previous 2 years attained meaningful weight loss with semaglutide, regardless of antidepressant use at baseline, in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.

Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.  

“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”

“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”

“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”

Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”

“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”

Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.

Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.

Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
 

36,000 Patients with obesity, 500 on antidepressants

Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.

However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.

The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.

The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.

Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m², or ≥27 kg/m² with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m² with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.

They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.

From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
• STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
• STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
• STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%. 

The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
• STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
• STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
• STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.

Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.

The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.

A version of this article appeared on Medscape.com.

Patients with obesity but without major depressive disorder or suicidal ideation within the previous 2 years attained meaningful weight loss with semaglutide, regardless of antidepressant use at baseline, in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.

Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.  

“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”

“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”

“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”

Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”

“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”

Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.

Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.

Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
 

36,000 Patients with obesity, 500 on antidepressants

Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.

However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.

The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.

The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.

Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m², or ≥27 kg/m² with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m² with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.

They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.

From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
• STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
• STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
• STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%. 

The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:

• STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
• STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
• STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
• STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.

Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.

The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.

A version of this article appeared on Medscape.com.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

For women who are obese, daily life is wrought with landmines. Whether it’s the challenges of air travel because plane seats are too small, the need to shield themselves from the world’s discriminating eyes, or the great lengths many will go to achieve better health and the promise of longevity, navigating life as an obese person requires a thick skin.

So, it’s no wonder so many are willing to pay more than $1,000 a month out of pocket to get their hands on drugs like semaglutide (Ozempic and Wegovy) or tirzepatide (Mounjaro). The benefits of these drugs, which are part of a new class called glucagonlike peptide–1 (GLP-1) receptor agonists, include significant and rapid weight loss, blood sugar control, and improved life quality; they are unprecedented in a setting where surgery has long been considered the most effective long-term option.

On the flip side, the desire for rapid weight loss and better blood sugar control also comes with an unexpected cost. Many women living with obesity who take oral contraceptives are unaware that these drugs – especially Mounjaro – can interfere with the absorption of birth control pills and how well they work, making an unintended pregnancy more likely.

Neel Shah, MD, an endocrinologist and associate professor at the University of Texas Health Science Center at Houston, said he has had several patients become pregnant without intending to. 

“It was when Mounjaro came out on the market when we started using it,” he said of the drug the Food and Drug Administration approved for type 2 diabetes in 2022. “It [the warning] was in the product insert, but clinically speaking, I don’t know if it was at the top of providers’ minds when they were prescribing Mounjaro.”

When asked if he believed that we were going to be seeing a significant increase in so-called Mounjaro babies, Dr. Shah was sure in his response. 

“Absolutely. We will because the sheer volume [of patients] will increase,” he said.
 

It’s all in the gut

One of the ways that drugs like Mounjaro work is by delaying the time that it takes for food to move from the stomach to the small intestine. Although data are still evolving, it is believed that this process – delayed gastric emptying – may affect the absorption of birth control pills. 

Dr. Shah said another theory is that vomiting, which is a common side effect of these types of drugs, also affects the pills’ ability to prevent pregnancy. 

And “there’s a prolonged period of ramping up the dose because of the GI side effects,” said Pinar Kodaman, MD, PhD, a reproductive endocrinologist and assistant professor of gynecology at Yale University in New Haven, Conn. 

“Initially, at the lowest dose, there may not be a lot of potential effect on absorption and gastric emptying. But as the dose goes up, it becomes more common, and it can cause diarrhea, which is another condition that can affect the absorption of any medication,” she said.
 

Unanticipated outcomes, extra prevention

Roughly 42% of women in the United States are obese, 40% of whom are between the ages of 20 and 39. Although these new drugs can improve fertility outcomes for women who are obese (especially those with polycystic ovary syndrome, or PCOS), only one – Mounjaro – currently carries a warning about birth control pill effectiveness on its label. Unfortunately, it appears that some doctors are unaware or not counseling patients about this risk, and the data are unclear about whether other drugs in this class, like Ozempic and Wegovy, have the same risks. 

“To date, it hasn’t been a typical thing that we counsel about,” said Dr. Kodaman. “It’s all fairly new, but when we have patients on birth control pills, we do review other medications that they are on because some can affect efficacy, and it’s something to keep in mind.”

It’s also unclear if other forms of birth control – for example, birth control patches that deliver through the skin – might carry similar pregnancy risks. Dr. Shah said some of his patients who became pregnant without intending to were using these patches. This raises even more questions, since they deliver drugs through the skin directly into the bloodstream and not through the GI system. 

What can women do to help ensure that they don’t become pregnant while using these drugs? 

“I really think that if patients want to protect themselves from an unplanned pregnancy, that as soon as they start the GLP receptor agonists, it wouldn’t be a bad idea to use condoms, because the onset of action is pretty quick,” said Dr. Kodaman, noting also that “at the lowest dose there may not be a lot of potential effect on gastric emptying. But as the dose goes up, it becomes much more common or can cause diarrhea.” 

Dr. Shah said that in his practice he’s “been telling patients to add barrier contraception” 4 weeks before they start their first dose “and at any dose adjustment.”

Zoobia Chaudhry, an obesity medicine doctor and assistant professor of medicine at Johns Hopkins University in Baltimore, recommends that “patients just make sure that the injection and medication that they take are at least 1 hour apart.”

“Most of the time, patients do take birth control before bedtime, so if the two are spaced, it should be OK,” she said.

Another option is for women to speak to their doctors about other contraceptive options like IUDs or implantable rods, where gastric absorption is not going to be an issue. 

“There’s very little research on this class of drugs,” said Emily Goodstein, a 40-year-old small-business owner in Washington, who recently switched from Ozempic to Mounjaro. “Being a person who lives in a larger body is such a horrifying experience because of the way that the world discriminates against you.”

She appreciates the feeling of being proactive that these new drugs grant. It has “opened up a bunch of opportunities for me to be seen as a full individual by the medical establishment,” she said. “I was willing to take the risk, knowing that I would be on these drugs for the rest of my life.”

In addition to being what Dr. Goodstein refers to as a guinea pig, she said she made sure that her primary care doctor was aware that she was not trying or planning to become pregnant again. (She has a 3-year-old child.) Still, her doctor mentioned only the most common side effects linked to these drugs, like nausea, vomiting, and diarrhea, and did not mention the risk of pregnancy.

“Folks are really not talking about the reproductive implications,” she said, referring to members of a Facebook group on these drugs that she belongs to. 

Like patients themselves, many doctors are just beginning to get their arms around these agents. “Awareness, education, provider involvement, and having a multidisciplinary team could help patients achieve the goals that they set out for themselves,” said Dr. Shah. 

Clear conversations are key.

A version of this article first appeared on WebMD.com.

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

TOPLINE:

Nearly one in five adolescents are living with prediabetes, a condition where blood glucose levels are elevated, but are not high enough for a type 2 diabetes (T2D) diagnosis. According to a new study, higher levels of nonfasting glucose and hemoglobin A1c, and worsening obesity are important predictors of progression to T2D. In addition, metformin and weight stabilization may prove to be important interventions for preventing T2D in kids.

METHODOLOGY:

• Researchers did a retrospective chart review of patient data from Vanderbilt University Medical Center Pediatric Prediabetes Clinic, Nashville, Tenn., from May 2015 to August 2022.
• The study included 552 children with prediabetes, defined as abnormal blood glucose (fasting plasma glucose [FPG] ≥ 100 mg/dL, random glucose ≥ 150 mg/dL), or hemoglobin A1c equal to or greater than 5.9%.
• Based on follow-up visits, patients were classified as having progressed to T2D, or nonprogression.
• Researchers analyzed the patients’ initial visit A1c, fasting C-peptide, 2-hour glucose, fasting glucose, and body mass index (BMI), among other baseline characteristics.

TAKEAWAY:

• Thirty-six children (6.5%) progressed to T2D during the duration of the study period.
• The average time to T2D diagnosis was much longer in patients taking metformin (43 months), compared with those not taking the prescribed medication (28 months).
• Worsening obesity was strongly associated with T2D progression – patients who progressed to T2D had a higher BMI at baseline and had continued weight gain.
• A higher baseline A1c, fasting C-peptide, and 2-hour glucose were also associated with progression to T2D.
• In the multivariable analysis, both A1c and 2-hour glucose were strong independent predictors of progression.
• Fasting plasma glucose was not associated with progression to T2D.

IN PRACTICE:

“Weight stabilization and metformin therapy could be important interventions for diabetes prevention in children,” study author Ashley H. Shoemaker, MD, MSci, a pediatric endocrinologist at Vanderbilt University Medical Center in Nashville, Tenn., said in a press release.

In addition, A1c plus a nonfasting glucose may be a feasible way to identify high-risk pediatric patients in a clinical setting.
 

SOURCE:

This study was performed by Natasha Belsky, Jaclyn Tamaroff, and Ashley H. Shoemaker of the Vanderbilt University Medical Center and the Vanderbilt University School of Medicine in Nashville, Tenn. It was published October 12, 2023, in the Journal of the Endocrine Society

LIMITATIONS:

Additional patients who developed T2D may have been lost to follow-up, since the authors did not contact patients to confirm their disease status. The authors were also unable to establish racial differences in the progression to T2D because of missing data.

DISCLOSURES:

Funding for this study was provided by the National Center for Advancing Translational Sciences. One author has research contracts with Novo Nordisk and Boehringer Ingelheim.

A version of this article first appeared on Medscape.com.

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

A version of this article first appeared on Medscape.com.

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

A version of this article first appeared on Medscape.com.

Each additional decade of type 2 diabetes shortens lives by about 3.5 years, compared with not having diabetes, researchers estimate on the basis of data from studies conducted in 19 high-income countries.

They estimated that, among 50-year-olds, life expectancy of those diagnosed with type 2 diabetes at age 30 is 14 years shorter than that of their peers without diabetes. Among those diagnosed at age 50, life expectancy is 6 years shorter.

The study was recently published in The Lancet – Diabetes and Endocrinology.

The team analyzed data from the Emerging Risk Factors Collaboration and the UK Biobank. The data were from 97 long-term, prospective cohorts and involved 1.5 million participants who were followed for 23.1 million person-years.

“The strongest associations with earlier age at diagnosis of diabetes were for vascular (for example, myocardial infarction and stroke) and other causes of death – mainly respiratory, neurological, and infectious diseases and external causes,” they reported.

Their findings are consistent with previous studies that suggested that younger individuals who develop type 2 diabetes might have higher body mass index (BMI), blood pressure, and lipid levels and that they might experience faster deterioration in glycemic control than individuals who develop diabetes later, potentially leading to premature mortality.

Asked to comment, Anne Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, who was not involved with this study, said: “We’ve long known that diabetes reduces life expectancy, and the younger you get it the more years you lose. However, this study was from a broader and larger population base than prior studies.

“In this study, the major reason for death was vascular disease, and undertreatment of cardiovascular risk factors may have occurred in the younger individuals. We also don’t know about glucose control.

“I personally think the findings show that we should treat cardiovascular risk factors more aggressively in people diagnosed with [type 2] diabetes in their 30s and 40s,” urged Dr. Peters.
 

High priority should be given to prevention globally

“Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life,” senior author Emanuele Di Angelantonio, MD, PhD, from the University of Cambridge (England), explained in a press release. “As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

The findings suggest that “high priority should be given to developing and implementing interventions that prevent or delay the onset of [type 2 diabetes], especially as its prevalence among younger age groups is increasing globally,” the study authors wrote.

The results “support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism,” added co–senior author Naveed Sattar, MD, PhD, of the University of Glasgow,

Dr. Peters agreed: “People who develop type 2 diabetes at a younger age might have a different, potentially more aggressive type of type 2 diabetes and perhaps need treatment targets that are lower than people who develop type 2 diabetes when they are older.”

“The findings ... suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition,” Dr. Sattar said.

Dr. Peters added: “An issue for some is pregnancy. ... Many of the medications taken for management of CVD [cardiovascular disease] risk factors are contraindicated in pregnancy (as are many of the medications [for treating type 2 diabetes]).

“We need to be careful to risk reduce but take care of the ‘whole person,’ and if of childbearing age, consider the safest approaches to healthy management,” she emphasized.
 

Study results: Type 2 diabetes diagnosed at age 30, 40, and 50

Previous studies estimated that adults with type 2 diabetes die 6 years earlier on average in comparison with their counterparts who do not have diabetes, but it was not known how diabetes duration affects life span.

To investigate this, the team analyzed individual records from the Emerging Risk Factors Collaboration and the UK Biobank. The primary outcome was all-cause mortality. Other outcomes were deaths from CVD, cancer, and other causes.

Over a median follow-up of 12.5 years, there were 246,670 deaths: 84,443 from cardiovascular causes, 150, 972 from noncardiovascular causes, and 11,255 from unknown/ill-defined causes.

Compared with participants who did not have a history of type 2 diabetes, the hazard ratios for all-cause mortality, adjusted for age and sex, were 2.69 for participants diagnosed at age 30-39, 2.26 for those diagnosed aged 40-49, 1.84 aged 50-59, 1.57 for those aged 60-69, and 1.39 for those diagnosed 70 and older.

These hazard ratios were similar after adjusting for BMI, systolic blood pressure, and total cholesterol, but they were substantially attenuated after further adjusting for fasting glucose or hemoglobin A1c level.

Similar patterns were observed for cause-specific mortality.

“Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes,” the researchers wrote.

The study was funded the British Heart Foundation, the Medical Research Council, the National Institute for Health and Care Research, and Health Data Research UK. Dr. Peters is on advisory boards for Vertex, Eli Lilly, and Medscape, receives research funding from Abbott Diabetes Care and Insulet, and has stock options for Omada Health.

A version of this article first appeared on Medscape.com.

Young adults who developed type 2 diabetes as children often do not take medications to control blood pressure or cholesterol, according to a new study in JAMA Network Open. Researchers expressed alarm that young people who forgo these medications increase their chances of developing kidney disease or having a stroke.

“We’re learning more and more that those with youth onset [type 2 diabetes] really differ from those with adult onset: It looks like a more virulent form of the disease because kids are getting complications and comorbidities at much earlier ages and more severe levels,” said study author Paula Trief, PhD, a professor of psychiatry and behavioral science at State University of New York, Syracuse.

Participants in the new study were on average aged 26 years. They also had previously been part of the Treating Options for Type 2 Diabetes in Adolescents and Youth study, known as TODAY, which took place from 2004 to 2011. TODAY enrolled children between ages 10 and 17 years with type 2 diabetes who received either metformin, metformin plus rosiglitazone, or metformin plus a lifestyle intervention.

The study included extensive education and contact from medical professionals to the participants about managing diabetes.

“This cohort was followed a long time and they had a lot of support. It may be better than the real world where people haven’t had the history of this much attention,” said Lorraine Katz, MD, who specializes in endocrinology and diabetes at the Children’s Hospital of Philadelphia. Dr. Katz has enrolled participants in TODAY and published about medication adherence rates but was not part of the recent analysis.
 

Unannounced pill counts, addressing concerns about medication

The analysis, known as iCount, included 243 participants from the original TODAY study (159 girls) who had hypertension, neuropathy, or dyslipidemia that required ongoing medication. As the TODAY study was concluding between 2017 and 2019, researchers made unannounced phone calls to participants to request the numbers of pills they had prescribed, number of refills, and the refill date. Participants also counted aloud every pill in their possession twice.

Those phone calls continued for 3 consecutive months after iCount began and again at the same intervals 1 year later.

If the number of pills counted at a later time was at least 80% of the starting total, researchers considered this rate as low adherence. Anything less than 80% was considered high adherence.

“That’s kind of an arbitrary cutoff, but it’s one that’s used consistently in the literature” to measure medication adherence for many conditions including cancer and heart disease, Dr. Trief said. Unannounced calls to initiate pill counts were first used to understand how often people took medications for HIV, and this method was found to be a more reliable method than are self-reports.

Of 196 participants with hypertension or neuropathy, 157 (80.1%) had low adherence. And of the 146 people with high cholesterol, 137 (93.8%) had low adherence. Ninety-nine people with high cholesterol also had neuropathy or diabetes.

“This is new to the literature: We don’t really know as much about this age group,” because medication adherence studies of people who have had diabetes for more than a decade and are still in their 20s are rare, Dr. Katz said.

During the core TODAY study period, all medications were provided for free. In contrast, in the current study, participants had to obtain their prescriptions on their own. The researchers found that many participants who showed low adherence to blood pressure medications reported sometimes having trouble obtaining food (n = 62), struggling with securing stable housing (n = 47), or lacking reliable health care insurance (n = 28), all factors linked to medication adherence success, according to the analysis authors.

Researchers also assessed the impact of concerns that taking blood pressure medications may be harmful and found that people with these concerns were 37% less likely to maintain high adherence than others were by the 1-year follow-up point (odds ratio, 0.63; 95% confidence interval, 0.40-0.96; P = .01).

To some extent, the reasons people avoid medications are understandable, according to pediatric endocrinologist Tamara Hannon, MD, of Indiana University, Indianapolis.

“Rather than taking a medicine to feel better, you’re taking one not to have a problem in the future: You might not feel blood pressure, you certainly don’t feel cholesterol,” Dr. Hannon, who was not involved in the analysis, said. “Scolding them or telling them you’re going to be sorry one day doesn’t generally work.”

Dr. Hannon added that education alone about the benefits of medications does not generally drive people to adherence but that adding reminders to their phone calendar when refills are due could help. Or, the clinician could reach out to a trusted person in the patient’s life and enlist their support in taking medications consistently.

Dr. Trief advised that clinicians should carve out time for people to express their concerns about medications rather than simply writing a prescription and sending them on their way and to ask patients open-ended questions.

“If you just say to people do you have any questions, they usually say, ‘no.’ ”

No disclosures were reported.

A version of this article first appeared on Medscape.com.

Young adults who developed type 2 diabetes as children often do not take medications to control blood pressure or cholesterol, according to a new study in JAMA Network Open. Researchers expressed alarm that young people who forgo these medications increase their chances of developing kidney disease or having a stroke.

“We’re learning more and more that those with youth onset [type 2 diabetes] really differ from those with adult onset: It looks like a more virulent form of the disease because kids are getting complications and comorbidities at much earlier ages and more severe levels,” said study author Paula Trief, PhD, a professor of psychiatry and behavioral science at State University of New York, Syracuse.

Participants in the new study were on average aged 26 years. They also had previously been part of the Treating Options for Type 2 Diabetes in Adolescents and Youth study, known as TODAY, which took place from 2004 to 2011. TODAY enrolled children between ages 10 and 17 years with type 2 diabetes who received either metformin, metformin plus rosiglitazone, or metformin plus a lifestyle intervention.

The study included extensive education and contact from medical professionals to the participants about managing diabetes.

“This cohort was followed a long time and they had a lot of support. It may be better than the real world where people haven’t had the history of this much attention,” said Lorraine Katz, MD, who specializes in endocrinology and diabetes at the Children’s Hospital of Philadelphia. Dr. Katz has enrolled participants in TODAY and published about medication adherence rates but was not part of the recent analysis.
 

Unannounced pill counts, addressing concerns about medication

The analysis, known as iCount, included 243 participants from the original TODAY study (159 girls) who had hypertension, neuropathy, or dyslipidemia that required ongoing medication. As the TODAY study was concluding between 2017 and 2019, researchers made unannounced phone calls to participants to request the numbers of pills they had prescribed, number of refills, and the refill date. Participants also counted aloud every pill in their possession twice.

Those phone calls continued for 3 consecutive months after iCount began and again at the same intervals 1 year later.

If the number of pills counted at a later time was at least 80% of the starting total, researchers considered this rate as low adherence. Anything less than 80% was considered high adherence.

“That’s kind of an arbitrary cutoff, but it’s one that’s used consistently in the literature” to measure medication adherence for many conditions including cancer and heart disease, Dr. Trief said. Unannounced calls to initiate pill counts were first used to understand how often people took medications for HIV, and this method was found to be a more reliable method than are self-reports.

Of 196 participants with hypertension or neuropathy, 157 (80.1%) had low adherence. And of the 146 people with high cholesterol, 137 (93.8%) had low adherence. Ninety-nine people with high cholesterol also had neuropathy or diabetes.

“This is new to the literature: We don’t really know as much about this age group,” because medication adherence studies of people who have had diabetes for more than a decade and are still in their 20s are rare, Dr. Katz said.

During the core TODAY study period, all medications were provided for free. In contrast, in the current study, participants had to obtain their prescriptions on their own. The researchers found that many participants who showed low adherence to blood pressure medications reported sometimes having trouble obtaining food (n = 62), struggling with securing stable housing (n = 47), or lacking reliable health care insurance (n = 28), all factors linked to medication adherence success, according to the analysis authors.

Researchers also assessed the impact of concerns that taking blood pressure medications may be harmful and found that people with these concerns were 37% less likely to maintain high adherence than others were by the 1-year follow-up point (odds ratio, 0.63; 95% confidence interval, 0.40-0.96; P = .01).

To some extent, the reasons people avoid medications are understandable, according to pediatric endocrinologist Tamara Hannon, MD, of Indiana University, Indianapolis.

“Rather than taking a medicine to feel better, you’re taking one not to have a problem in the future: You might not feel blood pressure, you certainly don’t feel cholesterol,” Dr. Hannon, who was not involved in the analysis, said. “Scolding them or telling them you’re going to be sorry one day doesn’t generally work.”

Dr. Hannon added that education alone about the benefits of medications does not generally drive people to adherence but that adding reminders to their phone calendar when refills are due could help. Or, the clinician could reach out to a trusted person in the patient’s life and enlist their support in taking medications consistently.

Dr. Trief advised that clinicians should carve out time for people to express their concerns about medications rather than simply writing a prescription and sending them on their way and to ask patients open-ended questions.

“If you just say to people do you have any questions, they usually say, ‘no.’ ”

No disclosures were reported.

A version of this article first appeared on Medscape.com.

Young adults who developed type 2 diabetes as children often do not take medications to control blood pressure or cholesterol, according to a new study in JAMA Network Open. Researchers expressed alarm that young people who forgo these medications increase their chances of developing kidney disease or having a stroke.

“We’re learning more and more that those with youth onset [type 2 diabetes] really differ from those with adult onset: It looks like a more virulent form of the disease because kids are getting complications and comorbidities at much earlier ages and more severe levels,” said study author Paula Trief, PhD, a professor of psychiatry and behavioral science at State University of New York, Syracuse.

Participants in the new study were on average aged 26 years. They also had previously been part of the Treating Options for Type 2 Diabetes in Adolescents and Youth study, known as TODAY, which took place from 2004 to 2011. TODAY enrolled children between ages 10 and 17 years with type 2 diabetes who received either metformin, metformin plus rosiglitazone, or metformin plus a lifestyle intervention.

The study included extensive education and contact from medical professionals to the participants about managing diabetes.

“This cohort was followed a long time and they had a lot of support. It may be better than the real world where people haven’t had the history of this much attention,” said Lorraine Katz, MD, who specializes in endocrinology and diabetes at the Children’s Hospital of Philadelphia. Dr. Katz has enrolled participants in TODAY and published about medication adherence rates but was not part of the recent analysis.
 

Unannounced pill counts, addressing concerns about medication

The analysis, known as iCount, included 243 participants from the original TODAY study (159 girls) who had hypertension, neuropathy, or dyslipidemia that required ongoing medication. As the TODAY study was concluding between 2017 and 2019, researchers made unannounced phone calls to participants to request the numbers of pills they had prescribed, number of refills, and the refill date. Participants also counted aloud every pill in their possession twice.

Those phone calls continued for 3 consecutive months after iCount began and again at the same intervals 1 year later.

If the number of pills counted at a later time was at least 80% of the starting total, researchers considered this rate as low adherence. Anything less than 80% was considered high adherence.

“That’s kind of an arbitrary cutoff, but it’s one that’s used consistently in the literature” to measure medication adherence for many conditions including cancer and heart disease, Dr. Trief said. Unannounced calls to initiate pill counts were first used to understand how often people took medications for HIV, and this method was found to be a more reliable method than are self-reports.

Of 196 participants with hypertension or neuropathy, 157 (80.1%) had low adherence. And of the 146 people with high cholesterol, 137 (93.8%) had low adherence. Ninety-nine people with high cholesterol also had neuropathy or diabetes.

“This is new to the literature: We don’t really know as much about this age group,” because medication adherence studies of people who have had diabetes for more than a decade and are still in their 20s are rare, Dr. Katz said.

During the core TODAY study period, all medications were provided for free. In contrast, in the current study, participants had to obtain their prescriptions on their own. The researchers found that many participants who showed low adherence to blood pressure medications reported sometimes having trouble obtaining food (n = 62), struggling with securing stable housing (n = 47), or lacking reliable health care insurance (n = 28), all factors linked to medication adherence success, according to the analysis authors.

Researchers also assessed the impact of concerns that taking blood pressure medications may be harmful and found that people with these concerns were 37% less likely to maintain high adherence than others were by the 1-year follow-up point (odds ratio, 0.63; 95% confidence interval, 0.40-0.96; P = .01).

To some extent, the reasons people avoid medications are understandable, according to pediatric endocrinologist Tamara Hannon, MD, of Indiana University, Indianapolis.

“Rather than taking a medicine to feel better, you’re taking one not to have a problem in the future: You might not feel blood pressure, you certainly don’t feel cholesterol,” Dr. Hannon, who was not involved in the analysis, said. “Scolding them or telling them you’re going to be sorry one day doesn’t generally work.”

Dr. Hannon added that education alone about the benefits of medications does not generally drive people to adherence but that adding reminders to their phone calendar when refills are due could help. Or, the clinician could reach out to a trusted person in the patient’s life and enlist their support in taking medications consistently.

Dr. Trief advised that clinicians should carve out time for people to express their concerns about medications rather than simply writing a prescription and sending them on their way and to ask patients open-ended questions.

“If you just say to people do you have any questions, they usually say, ‘no.’ ”

No disclosures were reported.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Citing the strong overlap between heart disease, kidney disease, type 2 diabetes, and obesity, the American Heart Association has for the first time formally defined what they are calling cardiovascular-kidney-metabolic (CKM) syndrome.

“This work was prompted by the fact that CKM syndrome leads to premature morbidity and mortality, primarily because of a higher burden of CVD,” writing committee chair Chiadi Ndumele, MD, PhD, said in an interview.

“While CKM syndrome is a public health emergency, there is also great potential for improving CKM health in the population, with an increasing number of therapies that favorably impact metabolic risk factors, risk for adverse kidney events, or both, which also protect against CVD,” added Dr. Ndumele, director of obesity and cardiometabolic research in the division of cardiology at Johns Hopkins University, Baltimore.

The AHA presidential advisory and accompanying scientific statement, which provides a synopsis of evidence for the science and clinical management of CKM, were published online in the journal Circulation.
 

CKM syndrome staging

According to the AHA, one in three U.S. adults have three or more risk factors that contribute to CVD, metabolic disorders, and/or kidney disease.

In addition to defining CKM syndrome, the advisory provides a “staging construct, to be used in both adults and youth, that reflects the progressive pathophysiology and risk within CKM syndrome, with therapeutic guidance tied to CKM stages,” Dr. Ndumele told this news organization.

The AHA outlines four stages of CKM syndrome:

Stage 0: At this stage, no CKM risk factors are present, and the goal is to prevent CKM syndrome (particularly unhealthy weight gain) by achieving and maintaining ideal health based on the AHA’s Life’s Essential 8 recommendations. Adults in this stage should be screened every 3-5 years to assess lipids, blood pressure, and blood sugar.

Stage 1: At this stage, excess weight, abdominal obesity, or dysfunctional adipose tissue (clinically manifest as impaired glucose tolerance or prediabetes) is present without other metabolic risk factors or CVD. Management includes providing support for healthy lifestyle changes (healthy eating and regular physical activity), with a goal of at least 5% weight loss and addressing glucose intolerance if needed. Screening adults with stage 1 CKM every 2-3 years is advised to assess blood pressure, triglycerides, cholesterol, and blood sugar.

Stage 2: At this stage, metabolic risk factors (hypertriglyceridemia, hypertension, metabolic syndrome, diabetes) and kidney disease are present. The goal is to address risk factors to prevent progression to CVD and kidney failure. Screening for stage 2 CKM syndrome aligns with AHA/ACC guidelines, which include yearly assessment of blood pressure, triglycerides, cholesterol, blood sugar, and kidney function. More frequent kidney screening is recommended for individuals with increased risk of kidney failure based on kidney function assessments.

Stage 3: This stage describes individuals with subclinical CVD with metabolic risk factors or kidney disease or those at high predicted risk for CVD. The goal is to intensify efforts to prevent progression to symptomatic CVD and kidney failure. This may involve increasing or changing medications, and additional focus on lifestyle changes. Coronary artery calcium (CAC) measurement in some adults is recommended to assess narrowing of the arteries when treatment decisions are unclear.

Stage 4: Individuals with stage 4 CKM syndrome have symptomatic CVD, excess body fat, metabolic risk factors, or kidney disease. Stage 4 CKM syndrome is divided into two subcategories: (4a) no kidney failure and (4b) kidney failure. In this stage, patients may have already had a myocardial infarction (MI) or stroke or may already have heart failure. They also may have additional CV conditions such as peripheral artery disease or atrial fibrillation. The goal of care is individualized treatment for CVD with consideration for CKM syndrome conditions.

The advisory also describes CKM syndrome regression, “an important concept and public health message in which people making healthy lifestyle changes and achieving weight loss may regress to lower CKM syndrome stages and a better state of health,” the AHA says in a news release.

They note that a “critical” next step is to update the pooled cohort equation (PCE) risk prediction algorithm to include measures of kidney function, type 2 diabetes control, and social determinants of health for a more comprehensive risk estimate.

The advisory also recommends risk calculator updates be expanded to assess risk in people as young as age 30 and to calculate both 10- and 30-year CVD risk.

“Clearly defining the patient with CKM syndrome, and providing new approaches for CKM syndrome staging and risk prediction, will help health care professionals to identify these individuals earlier and to provide timely, holistic, and patient-centered care,” Dr. Ndumele said.

This presidential advisory was prepared by the volunteer writing group on behalf of the AHA . The authors have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.

HAMBURG, GERMANY – An upcoming joint society statement on hyperglycemic emergencies in adults with diabetes will de-emphasize glucose from the diagnostic criteria for diabetic ketoacidosis (DKA), along with many other updates to the last statement on the topic, published 14 years ago.  

Based on extensive literature reviews and observations of current trends, the new document – due to be published soon – will cover diagnosis and management of the two most serious acute hyperglycemic emergencies seen in adults, DKA and hyperosmolar hyperglycemic state (HHS).

New to the 2023 version will be a strong emphasis on the excess morbidity and mortality risks associated with the increasingly common “hybrid” presentation of the two conditions together, now seen in about a third of cases.

The new report will also more strongly urge clinicians to investigate why the person experienced the emergency.

While new-onset diabetes and infection are recognized precipitating causes for DKA, insulin omission related to finances, mental health, and social determinants should be identified, and patients directed to appropriate resources, said experts previewing the upcoming new report at the annual meeting of the European Association for the Study of Diabetes.

“The challenge is, although we were making progress for a long time in terms of those hyperglycemic crises, we’ve really plateaued and there are still people being admitted in large numbers, and when you look more globally even more so,” said American Diabetes Association Chief Science and Medical Officer Robert A. Gabbay, MD, PhD.

The new consensus report will be jointly endorsed by the ADA, the EASD, the American Association of Clinical Endocrinology, the Diabetes Technology Society, and the Joint British Diabetes Societies for Inpatient Care. The previous consensus statement on the subject was published in 2009 by the ADA alone.
 

New DKA and HHS definitions reflect emerging trends

The statement will revise the definition of DKA, partly spurred by the increasing occurrence and recognition of euglycemic ketoacidosis arising from the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors. For all patients with hyperglycemic crisis, the hyperglycemia cutoff is now lowered to 200 mg/dL (11.1 mmol/L) from the previous 250 mg/dL.

However, the glucose cutoff has been removed entirely for people with a history of diabetes.

“Both of these changes are recognizing the wide range of glucose levels at the presence of DKA. Approximately 10% of DKA occurs with euglycemia or near-normoglycemia,” noted coauthor Shivani Misra, MD, PhD, senior clinical lecturer and honorary consultant in Metabolic Medicine at Imperial College, London.

For assessing ketosis in DKA, the new statement strongly recommends use of beta-hydroxybutyrate – either via point-of-care test or serum level measured in a laboratory – with a low cutoff of ≥ 3.0 mmol/L. Alternatively, a urine ketone strip value of 2+ or greater can be used.

However, beta-hydroxybutyrate testing is more widely available now than it was in 2009 and is strongly preferred over urine ketone measurement because it’s the predominant ketone during acidosis. Moreover, urine acetoacetate – measured by the strips – paradoxically increases during resolution of DKA, and drug interferences can occur with urine ketone measurement, Dr. Misra noted.

Metabolic acidosis is now defined as a pH < 7.3 and/or a bicarbonate concentration < 18 mmol/L, up from 15 in some prior guidelines including the United Kingdom’s. Also, anion gap has been removed from the main definition but, the document will say, can still be used in settings where ketone testing is unavailable.

As previously, the new statement will classify DKA by mild, moderate, and severe but now for the first time there are recommendations of care for each of those levels, as well as for HHS.

For HHS, the glucose cutoff of ≥ 600 mg/dL will stay the same. But now, the effective serum osmolality has been lowered from > 320 to > 300 mOsml/L to account for the effect of dehydration, along with an alternative criteria of total serum osmolality > 320 mOsm/L. The same two changes as with DKA for both ketones and acidosis have also been included for HHS.

Asked to comment, session audience member and independent diabetes industry consultant Charles Alexander, MD, told this news organization, “I liked the proposal to eliminate the anion gap in decision-making and to focus on measurement of blood ketones, principally beta-hydroxybutyrate, in the diagnosis of DKA and monitoring the effect of treatment.

“If someone is on an SGLT2 inhibitor, there is no need to look at blood glucose levels, which may be normal or near normal in the setting of DKA.”

But Dr. Alexander thinks that they should have eliminated glucose levels entirely as part of the DKA/HHS definition even for people without diabetes.

“The problem is that medical education for many years has taught us that DKA is a condition of high blood glucose, but it may not be. It is good that they said blood glucose levels were not important if the patient had a history of diabetes. However, a glucose of 200mg/dL may not be low enough if someone is on an SGLT2 inhibitor. There needs to be a much lower threshold for measuring blood ketones in anyone with nausea, vomiting, and abdominal pain, regardless of the blood glucose level.”
 

Acute management: IV fluids, insulin, and potassium

Like the 2009 statement, the new one will include detailed management flowcharts for DKA and HHS, but this time in color. This new statement includes individual algorithms for management with intravenous fluids, insulin, and potassium. Bicarbonate has been removed and relegated to a note at the bottom saying that it should only be considered if pH is < 7.0.

Under fluid treatment, the new statement offers more information about using crystalloids to treat dehydration and a recommendation to add dextrose to IV fluid therapy as a substrate when the glucose drops below 250 mg/dL, in order to prevent hypoglycemia. For euglycemic DKA, the recommendation is to include dextrose and normal saline simultaneously.

And for the first time, subcutaneous rather than IV insulin is considered acceptable for mild, but not moderate or severe, DKA. 

Two options are suggested for IV insulin in HHS: The fluid can be given first and low-dose fixed-rate insulin infusion added, or fluids and insulin can be given at the same time.

Criteria for resolution of DKA are a venous pH of ≥ 7.3 or bicarbonate > 18 mmol/L, ketones < 0.6 mmol/L, and glucose ideally < 200 mg/dL (11.0 mmol/L). For HHS, resolution is suggested when the measured or calculated serum osmolality falls to < 300 mosm/kg, blood glucose is < 250mg/dL (13.9 mmol/L), urine output > 0.5 mL/kg/hour, and cognitive status is improved.

The statement also will provide detailed recommended options for transitioning from IV to subcutaneous insulin, but defers to clinical judgment for deciding when the patient can be discharged. The initiation or continuation of SGLT2 inhibitors is not recommended at any time during hospitalization for hyperglycemic crises.
 

Mitigating complications, preventing recurrence

In addition to listing potential complications of treating hyperglycemic crises, just as the 2009 statement did, the new one will offer mitigation strategies for some of the more common ones. For preventing hypoglycemia, frequent blood glucose monitoring is advised along with adding dextrose to the IV fluids when glucose drops below 250 mg/dL.

For prevention of hypokalemia, which occurs in about half of patients treated for DKA and HHS, the statement recommends potassium monitoring every 4 hours and replacement added to fluids.

Acute kidney injury, also occurring in about half of people treated for DKA and/or HHS, usually resolves with hydration. Daily renal function monitoring is advised.
 

Preventing recurrence: Many factors beyond clinical

Prevention of recurrence with readmission for DKA and/or HHS, occurring in up to 22% of U.S. patients within 30 days, entails close follow-up within 2-4 weeks after discharge (including via telemedicine), and assessment of possible causes, including mental health disorders and social determinants of health.

Appropriate education should be provided, including “structured education” involving problem-solving, sick day rules, injection techniques, a review of insulin doses, consideration of continuous glucose monitoring (CGM), and home ketone testing.  

Patients should be provided with an adequate supply of insulin and durable diabetes equipment, along with contact information for health care professionals who can assist them. Social service professionals can be helpful for patients who lack reliable access.

Dr. Gabbay told this news organization, “The eye-opening thing is we tend to typically think of DKA as how people tend to get diagnosed with diabetes and, yes, that’s true, but that’s only a minority of people. Those might be preventable by early screening, but all these other people and the number of recurrent episodes, that’s an area where it’s really a failure of the system where we can do better in ensuring that doesn’t happen.”

Education is only part of it, he stressed. “It’s not just an intelligence thing. It’s social factors, and there can be complex psychological issues and mental health issues. We need to screen for those things when we see someone coming back the second, third, fifth, or sixth time. We’ve all seen that. Just educating them to take their insulin is not the answer. …You’ve got to ask the questions and engage them to go a little deeper.”

Dr. Gabbay is an employee of the ADA. Dr. Alexander has reported being a nonpaid advisor for diaTribe and a consultant for Kinexum. Dr. Misra has received speaker fees from Sanofi and ABCD and an investigator-initiated research grant from Dexcom, and is a trustee for the Diabetes Research and Wellness Foundation in the United Kingdom.

A version of this article appeared on Medscape.com.